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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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(R)-3-[18F]Fluoro-2-methyl-2-N-(methylamino)propanoic acid

(R)-[18F]NMeFAMP
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: July 29, 2010.

Chemical name:(R)-3-[18F]Fluoro-2-methyl-2-N-(methylamino)propanoic acidimage 96099761 in the ncbi pubchem database
Abbreviated name:(R)-[18F]NMeFAMP
Synonym:
Agent category:Compound
Target:L-type and A-type amino acid transporter
Target category:Transporter
Method of detection:Positron emission tomography (PET)
Source of signal:18F
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure for additional information in PubChem.

Background

[PubMed]

A variety of 11C- and 18F-labeled amino acids have been studied for potential use in positron emission tomography (PET) oncology (1, 2). Most brain tumors show an increased uptake of amino acids as compared with normal brain (3). These amino acids are composed of naturally occurring amino acids, such as l-[11C]leucine, l-[11C]methionine, and l-[11C]tyrosine, and non-natural amino acids, such as [11C]aminoisobutyric acid, [11C]1-aminocyclopentane-1-carboxylic acid, and [11C]1-aminocyclobutane-1-carboxylic acid. There are also 123I-labeled amino acids used in imaging in oncology (4-6).The natural amino acids are taken up by tumor cells through an energy-independent L-type amino acid transporter system and retained in tumor cells because of their higher metabolic pathways, including incorporation into proteins, than most normal cells (4). l-[11C]Methionine and [18F]fluorotyrosine have been widely used in the detection of tumors. On the other hand, the non-natural amino acids are not metabolized. Their uptakes are through both the L-type transporter and the energy-dependent A-type transporter (7). Therefore, they can accumulate intracellularly in high concentrations. [11C]Aminoisobutyric acid was shown to have a high tumor/background ratio (8, 9). (R)-3-[18F]Fluoro-2-methyl-2-N-(methylamino)propanoic acid ((R)-[18F]NMeFAMP) is a fluorinated analog of [11C]α-aminoisobutyric acid (AIB) that is being evaluated as a useful tracer in PET tumor imaging (10).

Synthesis

[PubMed]

Nucleophilic fluorination of (R)-3,4-dimethyl-1,2,3-oxathiazolidine-4-carboxylic acid tert-butyl ester 2,2-dioxide with K[18F]F/Kryptofix2.2.2 and subsequent hydrolysis and purification provided a radiosynthesis yield (decay-corrected) of 66% for (R)-[18F]NMeFAMP at the end of bombardment (10). A radiochemical purity of 99% was obtained. The total synthesis time was 85 min. The specific activity was ~1.85 GBq/µmol (50 mCi/µmol).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

(R)-[18F]NMeFAMP exhibited a rapidly increasing uptake into L9 rat gliosarcoma tumor cells with 7.08 ± 0.47% (n = 3) injected dose (ID)/5 × 105 cells at 30 min of incubation (10). The uptake was blocked by the presence of L-type transporter inhibitor BCH (2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid), A-type transporter inhibitor MeAIB (N-methyl-AIB), and system ASC inhibitor ACS (alanine-cysteine-serine) with 54%, 92%, and 89% inhibition, respectively. (S)-[18F]NMeFAMP (3.87 ± 0.22% ID/5 × 105 cells) exhibited a lower uptake than (R)-[18F]NMeFAMP. The uptake was blocked by the presence of BCH, MeAIB, and ACS with 29%, 79%, and 58% inhibition, respectively.

Animal Studies

Rodents

[PubMed]

Yu et al. (10) performed ex vivo biodistribution studies of (R)-[18F]NMeFAMP in rats (n = 5) implanted intracerebrally with a 9L gliosarcoma. The uptake in the brain (0.04% ID/g) was low at 30 min after injection and decreased slightly to 0.02% ID/g at 120 min. The uptake in the tumor was 1.46% ID/g at 15 min and increased to 2.78% ID/g at 120 min after injection. Most of the other tissues showed lower radioactivity levels at 120 min than at 15 min. The tissues with the highest accumulation at 30 min were the pancreas (2.72% ID/g) and kidney (8.91% ID/g). The tumor/brain ratios were 25.0, 53.2, 58.2, and 115.4 at 15, 30, 60, and 120 min, respectively. The radioactivity in the bone was low (0.44% ID/g at 120 min). (S)-[18F]NMeFAMP exhibited lower tumor accumulation but slightly higher pancreas and kidney accumulation than (R)-[18F]NMeFAMP. The tumor/brain ratios were 20.4, 30.2, 28.7, and 35.4 at 15, 30, 60, and 120 min, respectively. No blocking experiments were performed. The specificity of uptake, especially given the disruption of the blood brain barrier, was not studied.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Coleman R.E., Hoffman J.M., Hanson M.W., Sostman H.D., Schold S.C. Clinical application of PET for the evaluation of brain tumors. J Nucl Med. 1991;32(4):616–22. [PubMed: 2013802]
2.
Kaschten B., Stevenaert A., Sadzot B., Deprez M., Degueldre C., Del Fiore G., Luxen A., Reznik M. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med. 1998;39(5):778–85. [PubMed: 9591574]
3.
Herholz K., Heiss W.D. Positron emission tomography in clinical neurology. Mol Imaging Biol. 2004;6(4):239–69. [PubMed: 15262239]
4.
Jager P.L., Vaalburg W., Pruim J., de Vries E.G., Langen K.J., Piers D.A. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42(3):432–45. [PubMed: 11337520]
5.
Langen K.J., Pauleit D., Coenen H.H. 3-[(123)I]Iodo-alpha-methyl-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2002;29(6):625–31. [PubMed: 12234586]
6.
Lahoutte T., Caveliers V., Camargo S.M., Franca R., Ramadan T., Veljkovic E., Mertens J., Bossuyt A., Verrey F. SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation. J Nucl Med. 2004;45(9):1591–6. [PubMed: 15347729]
7.
Palacin M., Estevez R., Bertran J., Zorzano A. Molecular biology of mammalian plasma membrane amino acid transporters. Physiol Rev. 1998;78(4):969–1054. [PubMed: 9790568]
8.
Conti P.S., Sordillo P.P., Schmall B., Benua R.S., Bading J.R., Bigler R.E., Laughlin J.S. Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma. Eur J Nucl Med. 1986;12(7):353–6. [PubMed: 3792366]
9.
Fross R.D., Warnke P.C., Groothuis D.R. Blood flow and blood-to-tissue transport in 9L gliosarcomas: the role of the brain tumor model in drug delivery research. J Neurooncol. 1991;11(3):185–97. [PubMed: 1823340]
10.
Yu W., McConathy J., Williams L., Camp V.M., Malveaux E.J., Zhang Z., Olson J.J., Goodman M.M. Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-3-[(18)F]fluoro-2-methylpropanoic acid (FAMP) and (R)- and (S)-3-[(18)F]fluoro-2-methyl-2-N-(methylamino)propanoic acid (NMeFAMP) as potential PET radioligands for imaging brain tumors. J Med Chem. 2010;53(2):876–86. [PMC free article: PMC2836592] [PubMed: 20028004]

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